Neoadjuvant PD-1 blockade in patients with resectable desmoplastic melanoma (SWOG 1512).
Authors: Kari Lynn Kendra, James Moon, Zeynep Eroglu, Siwen Hu-Lieskovan, William Edgar Carson, David A. Wada, Jose A Plaza, Gino Kim In, Alexandra Ikeguchi, John Robert Hyngstrom, Andrew Scott Brohl, Bartosz Chmielowski, Nikhil I. Khushalani, Joseph Markowitz, Marcus Monroe, Kenneth F. Grossmann, Vernon K. Sondak, Elad Sharon, Michael Wu, Antoni Ribas
Journal: Journal of Clinical Oncology (2022)

9502 Background: Desmoplastic melanoma (DM) is a rare cancer defined by a dense fibrous collagen matrix. It is associated with high UV exposure leading to a high mutational load. When locally advanced, the standard of care is wide excision and radiation therapy due to its propensity for local relapses. Metastatic DM has a high response rate (RR) to PD-1 blockade therapy (Eroglu et al. Nature 2018). We hypothesized that neoadjuvant treatment with anti-PD-1 monotherapy may induce pathologically confirmed regressions in a high percentage of cases, potentially allowing for less extensive local treatment. Methods: Patients &gt; 18 years old with histologically confirmed resectable (primary, recurrent, or regional lymph node metastasis) DM with clinical evidence of residual disease received pembrolizumab 200 mg q3 weeks (wk) 3 followed by excision. No adjuvant therapy was administered. Primary endpoint: pathological complete response (pCR), with the assumption that pCR of 25% would be considered a positive result worthy of future study. To test this hypothesis, a single arm trial with 25 eligible patients would have a 3.4% probability of a positive result with a true pCR of 5%, and a power of 90% of a positive result if the true pCR is 25%. Secondary endpoints: clinical RR by imaging and clinical exam, median overall survival (OS), and evaluation of safety/tolerability of neoadjuvant pembrolizumab. Adverse events were assessed q3 wk. Disease assessments occurred at baseline and q9 wk. NCT02775851. Results: We enrolled-29 eligible patients with resectable DM. One patient refused treatment and was omitted from further analysis. Median age was 75, 79% were male, primary sites of disease were 72% H&amp;N, 10% torso, 14% extremities, 3% unknown. No patients received prior systemic therapy. Mean time from C1D1 treatment to surgery was 84.2 (range: 52-135) days, mean number of cycles received 3.3 (range: 2-4). 26/27 (93%) of patients underwent wide excision of the resectable disease, of which 14 (54%) underwent sentinel lymph node biopsy. One patient underwent resection of a nodal recurrence thus did not require wide excision. pCR was noted in 15/27 (56%) of patients (95% CI: 35%-75%). One patient without a pCR had a major pathologic response with 0.2 mm residual melanoma. In addition, one patient with a clinical CR did not undergo resection by choice. None became inoperable. Clinical RR was 52% (95% CI: 32%-71%). Median OS has not been reached, with two nontreatment related deaths (acute hypoxic respiratory failure; unknown). No &gt; grade 2 related adverse events were observed. Conclusions: Neoadjuvant pembrolizumab in resectable DM results in a high pCR rate with excellent tolerance, which supports consideration of PD-1 blockade therapy prior to surgery. Funding: U10CA180888 and U10CA180819; and in part by Merck Sharp &amp; Dohme Corp., a subsidiary of Merck &amp; Co., Inc., Kenilworth, NJ, USA. Clinical trial information: NCT02775851.